ArticleFrontiers in immunology2023
Expression of HMGCS2 in intestinal epithelial cells is downregulated in inflammatory bowel disease associated with endoplasmic reticulum stress.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Loss of E3 ligase Ube4A Disrupts Colon Homeostasis and Accelerates Experimental Colitis via Altered Lipid Handling.bioRxiv : the preprint server for biology · 2026Article
- Ketone ester supplementation protects from experimental colitis via improved goblet cell differentiation and function.European journal of nutrition · 2025Article
- Causal Relationship Between Mitochondrial Characteristics and Inflammatory Bowel Disease and Its Subtypes: Evidence for Mendelian Randomization.JGH open : an open access journal of gastroenterology and hepatology · 2025Article
- Toward Precision Medicine: Molecular Biomarkers of Response to Tofacitinib in Inflammatory Bowel Disease.Genes · 2025Review
- Spatial transcriptomics delineates potential differences in intestinal phenotypes of cardiac and classical necrotizing enterocolitis.iScience · 2025Article
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- Identification of Biomarkers Related to Liquid-Liquid Phase Separation for Ulcerative Colitis Based on Single-Cell and Bulk RNA Transcriptome Sequencing Data.Endocrine, metabolic & immune disorders drug targets · 2025Article
- HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis.Scientific reports · 2024Article
- Article
- Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose-induced cardiomyocyte injury.Immunity, inflammation and disease · 2024Article
- Colonic ketogenesis, a microbiota-regulated process, contributes to blood ketones and protects against colitis in mice.The Biochemical journal · 2024Article
- The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
23 authors at 12 institutions in 3 countries.
Funding
Abstract
Introduction: The Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease. Methods: We analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli. Several genes were further analyzed in colonic biopsies from Ulcerative Colitis patients and healthy controls. Lastly, we generated Caco-2 cells lacking HMGCS2 by CRISPR Cas-9 and analyzed the functional implications of its absence in Intestinal Epithelial Cells. Results: Exposure to a TLR ligand after thapsigargin treatment resulted in a powerful synergistic modulation of gene expression, which led us to identify new genes and pathways that could be involved in inflammatory responses linked to the Unfolded Protein Response. Key differentially expressed genes in the array also exhibited transcriptional alterations in colonic biopsies from active Ulcerative Colitis patients, including NKG2D ligands and the enzyme HMGCS2. Moreover, functional studies showed altered metabolic responses and epithelial barrier integrity in HMGCS2 deficient cell lines. Conclusion: We have identified new genes and pathways that are regulated by the Unfolded Protein Response in the context of Inflammatory Bowel Disease including
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